The overall goal of this project is to identify breast cancer susceptibility genes and to elucidate how they interact with epidemiological risk factors to cause this malignancy. This work is geared towards the African-American population, which has been scarcely studied and has shown an increase in the incidence of breast cancer in recent times, especially in younger women. The project has four complementary components. The core component is a family study which will address for the first time the issue of interactions between genetic susceptibility and epidemiological risk factors of breast cancer in a hospital based series of family data. This will involve collecting systematically a sample of 250-300 families through all new breast cancer patients treated at Howard University Hospital. The recorded information will include: a detailed clinical and histological description of the tumor, the identification of the patient's first and second degree relatives. The familial analysis will be conducted by the relevant statistical models, to test for specific genetic hypotheses while accounting for various risk factors and other sources of familial covariation. The second component, a case/control study, using hospital, neighborhood, and sister controls, will determine the risk factors associated with breast cancer which are relevant to the African-American population. Comparisons will be made with risk factors already identified among Caucasians. The third component, loss of hererozygosity analysis in tumor/blood pairs from breast cancer patients, will identify chromosomal regions which may harbor breast cancer susceptibility genes. The las component involves the mapping of breast cancer genes by linkage analysis in multiple-case families. The chromosomal location of breast cancer genes and the understanding of how these genes interact with environment in tumorigenesis will have direct significance in counseling and prevention.